Highly stereoselective multigram scale synthesis of (3S,4S)-Statine and (3S,4S)-N-Benzylstatine

Abstract

Statins are essential naturally occurring β-hydroxy-γ-amino acids and (3S,4S)-Statine, derived from L-Leucine, is found in important aspartic proteases inhibitors like Pepstatin A. We developed a new synthesis of (3S,4S)-Statine based on the highly diastereoselective reduction of N,N-Boc/Benzyl protected β-ketoester intermediate. This Boc/Benzyl protection strategy gives access to either N-Fmoc or N-Benzyl protected (3S,4S)-Statine on multigram scale quantities.

Keywords

• Statine
• β-ketoester reduction
• N-alkylated peptides
• Aspartic protease inhibitors
• L-leucine